Growth factors capable of stimulating DNA synthesis and cell division have been isolated from rat chondrosarcoma and from bovine and human cartilage. In these tissues, growth factor activity is found in both the cells and in the extracellular matrix (ECM). Cellular growth factor activity is found to be predominantly associated with the chromatin fraction and can be eluted from chromatin with 0.25 to 0.75 M NaCl. The cellular growth factors are highly cationic with isoelectric points between 9.5 and 10. They have molecular weights in the range of 14,000 and 18,000. The ECM of both cartilage and chondrosarcoma contain the cationic growth factor found on chromatin and at least one noncationic growth factor species. The cationic cellular and ECM-derived growth factors have been purified to a high degree by a combination of preparative cationic exchange chromatography on Biorex 70, size exclusion chromatography on Sephadex G-100 and HPLC TSK columns and cationic exchange on HPLC CM 300 columns. Highly purified chondrosarcoma and cartilage-derived growth factors stimulate DNA synthesis in 3T3 cells at concentrations of 10 ng/ml and less. These growth factors are also mitogenic for cell strains, in particular chondrocytes and capillary endothelial cells. They are not mitogenic for aortic endothelial cells or smooth muscle cells. The ability of the cartilage and chondrosarcoma-derived growth factors to stimulate both the migration and proliferation of capillary endothelial cells suggests that they may be involved in normal and tumor-induced angiogenesis. Monoclonal antibodies have been prepared against the cartilagederived growth factor (CDGF) and when coupled to a solid support are capable of purifying CDGF by affinity chromatography. The goals of the research are: (1)\To complete the purification of all the growth factor species found in cartilage and chondrosarcoma. (2)\To make antibodies against the chondrosarcoma-derived growth factors. These antibodies will be used to detect and localize growth factor in animals carrying chondrosarcoma in vivo. (3)\To determine if the growth factors are capable of inducing angiogenesis in vivo. (4)\To administer growth factor preparations to animals in vivo via sustained release polymers. (5)\To investigate the nature of the interaction of growth factor with chromatin.